目的 评价益生菌对孤独谱系障碍(ASD)患者核心症状的治疗效果,为ASD的治疗和干预提供理论依据。方法 计算机检索中国生物医学文献服务系统(SinoMed)、万方数据知识服务平台、维普引文数据库和中国知网,英文数据库包括PubMed、Embase和Web of Science共7个数据库中有关益生菌干预孤独谱系障碍患者核心症状影响的文献,检索期限为2000年1月到2023年5月。采用Rev Man5.4进行Meta分析,计算效应量合并异质性检验敏感性分析和亚组分析。结果 共纳入10项研究343名患者。Meta分析显示,对于ASD核心症状得分干预组与对照组间差异有统计学意义(SMD=-0.34, 95%CI:-0.55~-0.12, P＜0.05),亚组分析显示,在亚洲人种中展开的试验疗效不显著(SMD=-0.32, 95%CI:-0.63~0.00, P=0.05),而在高加索人种中疗效显著(SMD=-0.35, 95%CI:-0.65~-0.06, P＜0.02)。按年龄分组,发现包含成人的试验疗效不显著(SMD= -0.12, 95%CI:-0.57~0.33, P=0.61),只包含未成年人的试验中疗效显著(SMD=-0.40, 95%CI:-0.65~-0.16, P＝0.007)。按疗程分组,干预不超过3个月(SMD=-0.35, 95%CI:-0.66~-0.03, P＜0.05)和超过3个月(SMD=-0.33, 95% CI:-0.62~-0.03, P＜0.05)的疗效均显著。按菌株分组,单一菌群疗效不明显(SMD=-0.16, 95%CI:-0.46 ~0.15, P＞0.05),复合菌群疗效显著(SMD=-0.51, 95%CI:-0.81~-0.21, P＜0.05)。结论 益生菌治疗对于改善ASD患者的核心症状有效,但受人种、年龄和菌株等因素影响,在高加索人种、未成年人群中使用复合菌群的条件下有更好的疗效。
Abstract
Objective To evaluate the therapeutic effect of probiotics on core symptoms in patients with autism spectrum disorder (ASD), in order to provide theoretical basis for the treatment and intervention of ASD. Method Articles published from January 2000 to May 2023 on the effect of probiotics on core symptoms in ASD children were retrieved from 7 databases, including Chinese Biomedical Literature Service System (SinoMed), Wanfang Data Knowledge Service Platform, VIP Citation Database, and China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Web of Science.Meta-analysis was performed using RevMan 5.4.Effect size, combine heterogeneity test sensitivity analysis and subgroup analysis were calculated. Result Totally 10 studies with 343 patients were included in this Meta-analysis.Meta-analysis showed that there was statistically significant difference in ASD core symptom score between the intervention group and the control group (SMD=-0.34, 95%CI: -0.55 - -0.12, P<0.05).Subgroup analysis showed that the efficacy of the trial conducted in Asian populations was not significant (SMD=-0.32, 95%CI: -0.63 - 0.00, P=0.05).In Caucasian populations, the therapeutic effect was significant (SMD=-0.35, 95%CI: -0.65 - -0.06, P<0.05).Grouped by age, it was found that the efficacy was not significant in trials involving adults (SMD=-0.12, 95%CI: - 0.57 - 0.33, P=0.61), but significant in trials involving only minors (SMD=-0.40, 95%CI: -0.65 - -0.16, P<0.05).According to the treatment course grouping, the intervention for less than 3 months (SMD=-0.35, 95%CI: -0.66 - -0.03, P<0.05) and more than 3 months (SMD=-0.33, 95%CI: -0.62 - -0.03, P<0.05) showed significant therapeutic efficacy.Grouped by bacterial strains, the efficacy of a single microbial community was not significant (SMD=-0.16, 95%CI: -0.46 - 0.15, P>0.05), while the efficacy of a composite microbial community was significant (SMD=-0.51, 95%CI: -0.81 - -0.21, P<0.05). Conclusions Probiotic therapy is effective in improving the core symptoms of ASD patients, but is influenced by factors such as race, age and probiotic strain. Composite microbiota has better efficacy in Caucasian and underage populations.
关键词
孤独症谱系障碍 /
益生菌 /
核心症状 /
系统综述 /
Meta分析
Key words
autism spectrum disorder /
probiotics /
core symptoms /
systematic review /
Meta-analysis
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Elsabbagh M, Divan G, Koh YJ, et al.Global prevalence of autism and other pervasive developmental disorders[J].Autism Res,2012, 5(3): 160-179.
[2] 刘贤,林穗方,陈文雄,等.中国儿童孤独症谱系障碍患病率Meta分析[J].中国儿童保健杂志,2018, 26(4): 371-375.
Liu X, Lin SF, Chen WX, et al.Meta-analysis of the prevalence of autism spectrum disorders in Chinese children[J].Chin J Child Health Care,2018, 26(4): 371-375.(in Chinese)
[3] Maenner MJ, Warren Z, Williams AR, et al.Prevalence and characteristics of autism spectrumdisorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2020[J].MMWR Surveill Summ, 2023, 72(2): 1-14.
[4] 中国残疾人联合会.中国0~6岁残疾儿童抽样调查报告[M].中国统计出版社,2003.
[5] Lavelle TA, Weinstein MC, Newhouse JP, et al.Economic burden of childhood autism spectrum disorders[J].Pediatrics, 2014, 133(3): e520-e529.
[6] Hume K, Steinbrenner JR, Odom SL, et al.Evidence-based practices for children, youth, and young adults with autism: Third generation review[J].J Autism Dev Disord, 2021, 51(11): 4013-4032.
[7] Biswas M, Vanwong N, Sukasem C.Pharmacogenomics in clinical practice to prevent risperidone-induced hyperprolactinemia in autism spectrum disorder[J].Pharmacogenomics, 2022, 23(8): 493-503.
[8] Houghton R, van den Bergh J, Law K, et al.Risperidone versus aripiprazole fracture risk in children and adolescents with autism spectrum disorders[J].Autism Res, 2021, 14(8): 1800-1814.
[9] Hara Y, Ago Y,Taruta A, et al.Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice[J].Psychopharmacology (Berl),2017, 234(21): 3217-3228.
[10] Parracho HMRT, Gibson GR, Knott F, et al.A double-blind, placebo-controlled, crossover-designed probiotic feeding study in children diagnosed with autistic spectrum disorders[J].International Journal of Probiotics & Prebiotics, 2010, 5(2): 69-74.
[11] Santocchi E, Guiducci L, Prosperi M, et al.Effects of probiotic supplementation on gastrointestinal, sensory and core symptoms in autism spectrum disorders: A randomized controlled trial[J].Front Psychiatry, 2020, 11: 550593.
[12] Schmitt LM, Smith EG, Pedapati EV, et al.Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder[J].Sci Rep, 2023, 13(1): 5192.
[13] Wang Y, Li N, Yang JJ, et al.Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder[J].Pharmacol Res, 2020, 157: 104784.
[14] Song W, Zhang M,Teng L, et al.Prebiotics and probiotics for autism spectrum disorder: A systematic review and meta-analysis of controlled clinical trials[J].J Med Microbiol, 2022, 71(4).
[15] He X, Liu W, Tang F, et al.Effects of probiotics on autism spectrum disorder in children: A systematic review and Meta-analysis of clinical trials[J].Nutrients, 2023, 15(6): 1415.
[16] Aman MG, Singh NN, Stewart AW, et al.Psychometric characteristics of the aberrant behavior checklist[J].Am J Ment Defic, 1985, 89(5): 492-502.
[17] Lord C,Rutter M, Dilavore P, et al.Autism diagnostic observation schedule: ADOS-2, Part 1: Modules 1-4[M].2nd ed.Los Angeles: Western Psychological Services, 2012.
[18] Janvier D, Choi YB, Klein C, et al.Brief report: Examining test-retest reliability of the Autism Diagnostic Observation Schedule (ADOS-2) Calibrated Severity Scores (CSS)[J].J Autism Dev Disord, 2022, 52(3): 1388-1394.
[19] Rutter M, Bailey A, Lord C.The Social Communication Questionnaire: Manual[M].Los Angeles: Western Psychological Services, 2003.
[20] American Psychiatric Association.Diagnostic and statistical manual of mentaldisorders[M].5th ed.Washington, DC: American Psychiatric Publishing, 2013.
[21] Billeci L, Callara A L, Guiducci L, et al.A randomized controlled trial into the effects of probiotics on electroencephalography in preschoolers with autism[J].Autism, 2023, 27(1): 117-132.
[22] Sherman HT, Liu K, Kwong K, Chan ST, et al. Carbon monoxide (CO) correlates with symptom severity, autoimmunity, and responses to probiotics treatment in a cohort of children with autism spectrum disorder (ASD): A post-hoc analysis of a randomized controlled trial[J]. BMC Psychiatry, 2022, 22(1): 536.
[23] Kong XJ, Liu J, Liu K, et al. Probiotic and oxytocin combination therapy in patients with autism spectrum disorder: A randomized, double-blinded, placebo-controlled pilot trial[J]. Nutrients, 2021, 13(5):1552.
[24] 李玉勤,孙映红,梁亚鹏,等.益生菌联合应用行为分析法治疗儿童孤独症谱系障碍的前瞻性随机对照研究[J].中国当代儿科杂志,2021, 23(11): 1103-1110.
Li YQ, Sun YH, Liang YP, et al.Effect of probiotics combined with applied behavior analysis in the treatment of children with autism spectrum disorder: A prospective randomized controlled trial[J].Chin J Contemp Pediatr, 2021, 23(11): 1103-1110.(in Chinese)
[25] Arnold LE, Luna RA, Williams K, et al.Probiotics for gastrointestinal symptoms and quality of life in autism: A Placebo-controlled pilot trial[J].J Child Adolesc Psychopharmacol, 2019, 29(9): 659-669.
[26] Sanctuary MR,Kain JN, Chen SY, et al.Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms[J].PLoS One, 2019, 14(1): e210064.
[27] Liu Y W, Liong M T, Chung Y E, et al. Effects of lactobacillus plantarum PS128 on children with autism spectrum disorder in Taiwan: A randomized, double-blind, placebo-controlled trial[J]. Nutrients, 2019, 11(4): 820.
[28] Sharon G, Sampson TR,Geschwind DH, et al.The central nervous system and the gut microbiome[J].Cell, 2016, 167(4): 915-932.
[29] Mayer EA, Knight R,Mazmanian SK, et al.Gut microbes and the brain: Paradigm shift in neuroscience[J].J Neurosci, 2014, 34(46): 15490-15496.
[30] Yatsunenko T, Rey FE, Manary MJ, et al.Human gut microbiome viewed across age and geography[J].Nature, 2012, 486(7402): 222-227.
[31] Deschasaux M, Bouter KE, Prodan A, et al.Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography[J].Nat Med, 2018, 24(10): 1526-1531.
[32] Obregon-Tito AJ, Tito RY, Metcalf J, et al.Subsistence strategies in traditional societies distinguish gut microbiomes[J].Nat Commun, 2015, 6: 6505.
[33] Mazurak N, Broelz E, Storr M, et al.Probiotic therapy of the irritable bowel syndrome: Why is the evidence still poor and what can be done about it?[J].J Neurogastroenterol Motil, 2015, 21(4): 471-485.
[34] Buffington SA, Di Prisco GV, Auchtung TA, et al.Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring[J].Cell, 2016, 165(7): 1762-1775.
[35] Muhammad F, Fan B, Wang R, et al.Themolecular gut-brain axis in early brain development[J].Int J Mol Sci, 2022, 23(23): 236-241.
PDF(1804 KB)
